{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T08:32:26Z","timestamp":1775118746603,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The fimbrin protein family contains a variety of proteins, among which Plastin1 (PLS1) is an important member. According to recent studies, variations in the coding region of the PLS1 gene are associated with the development of deafness. However, the molecular mechanism of deafness caused by\n                    <jats:italic>PLS1<\/jats:italic>\n                    gene variants remains unknown. Whole\u2010exome sequencing was performed on hearing\u2010impaired family members and hearing family members to identify pathogenic variants, followed by Sanger sequencing. A minigene assay was conducted to investigate the effect of the variant on\n                    <jats:italic>PLS1<\/jats:italic>\n                    mRNA splicing. The pathogenicity of the variant was further investigated in zebrafish. RNA\u2010sequencing (RNA\u2010seq) was performed to analyze the dysregulation of downstream signaling pathways caused by knockdown of\n                    <jats:italic>PLS1<\/jats:italic>\n                    expression. We identified a novel variant,\n                    <jats:italic>PLS1<\/jats:italic>\n                    c.981+1G&gt;A, in a large Chinese family with hearing loss and showed that the variant is responsible for the occurrence of hearing loss by inducing exon 8 skipping. The variant caused abnormal inner ear phenotypes, characterized by decreases in the mean otolith distance, anterior otolith diameter, posterior otolith diameter, cochlear diameter, and swimming speed and distance in zebrafish. Furthermore, silencing\n                    <jats:italic>PLS1<\/jats:italic>\n                    expression significantly upregulated the expression of genes in the PI3K\u2010Akt signaling pathway, including\n                    <jats:italic>Col6a3<\/jats:italic>\n                    ,\n                    <jats:italic>Spp1<\/jats:italic>\n                    ,\n                    <jats:italic>Itgb3<\/jats:italic>\n                    and hepatocyte growth factor (\n                    <jats:italic>Hgf<\/jats:italic>\n                    ).\n                    <jats:italic>PLS1<\/jats:italic>\n                    c.981+1G&gt;A is a novel pathogenic variant causing hearing loss by inducing exon 8 skipping. Upregulation of the expression of genes in the PI3K\u2010Akt signaling pathway plays an important role in the pathogenesis caused by variants in the\n                    <jats:italic>PLS1<\/jats:italic>\n                    gene.\n                  <\/jats:p>","DOI":"10.1111\/cge.14283","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T03:55:26Z","timestamp":1671508526000},"page":"413-423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel\n                    <scp>PLS1<\/scp>\n                    c.981+\n                    <scp>1G<\/scp>\n                    &gt;A variant causes autosomal\u2010dominant hereditary hearing loss in a family"],"prefix":"10.1111","volume":"103","author":[{"given":"Liangpu","family":"Xu","sequence":"first","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinrui","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect  Fuzhou China"},{"name":"Medical Research Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics &amp; Gynecology and Pediatrics Fujian Medical University  Fuzhou China"},{"name":"NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non\u2010human Primates Fujian Maternity and Child Health Hospital  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"BGI Genomics BGI\u2010Shenzhen  Shenzhen China"},{"name":"Hebei Industrial Technology Research Institute of Genomics in Maternal &amp; Child Health Shijiazhuang BGI Genomics Co., Ltd.  Shijiazhuang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingji","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect  Fuzhou China"},{"name":"Medical Research Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics &amp; Gynecology and Pediatrics Fujian Medical University  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyi","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College Guangxi Medical University  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4475-531X","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"BGI Genomics BGI\u2010Shenzhen  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7789-6907","authenticated-orcid":false,"given":"Pengcheng","family":"Yao","sequence":"additional","affiliation":[{"name":"BGI Genomics BGI\u2010Shenzhen  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihua","family":"Tan","sequence":"additional","affiliation":[{"name":"BGI Genomics BGI\u2010Shenzhen  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si","family":"Zhou","sequence":"additional","affiliation":[{"name":"BGI Genomics BGI\u2010Shenzhen  Shenzhen China"},{"name":"Hebei Industrial Technology Research Institute of Genomics in Maternal &amp; Child Health Shijiazhuang BGI Genomics Co., Ltd.  Shijiazhuang China"},{"name":"College of Life Sciences University of Chinese Academy of Sciences  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yali","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical Technology and Engineering College of Fujian Medical University  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolan","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Otolaryngological Department of Fujian Maternity and Child Health Hospital Affiliated Hospital of Fujian Medical University  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Lin","sequence":"additional","affiliation":[{"name":"Medical Genetic Diagnosis and Therapy Center of Fujian 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Non\u2010human Primates Fujian Maternity and Child Health Hospital  Fuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Hereditary Hearing Loss and its Syndromes","author":"Gorlin RJ","year":"1995"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.17647"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-018-1880-5"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0285-0"},{"issue":"6","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00439-018-1895-y","article-title":"A dominant variant in the PDE1C gene is associated with nonsyndromic hearing loss","volume":"137","author":"Wang L","year":"2018","journal-title":"Hum 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